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KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers

SIMPLE SUMMARY: It is well known that dark-coated dogs, especially schnauzers, have a predisposition for digital squamous cell carcinoma (dSCC). Molecular genetic studies by other researchers indicate a pathogenetic role of copy number variations (CNVs) of the KIT ligand (KITLG) gene. Our study aime...

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Autores principales: Aupperle-Lellbach, Heike, Heidrich, Daniela, Kehl, Alexandra, Conrad, David, Brockmann, Maria, Törner, Katrin, Beitzinger, Christoph, Müller, Tobias
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966798/
https://www.ncbi.nlm.nih.gov/pubmed/36851451
http://dx.doi.org/10.3390/vetsci10020147
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author Aupperle-Lellbach, Heike
Heidrich, Daniela
Kehl, Alexandra
Conrad, David
Brockmann, Maria
Törner, Katrin
Beitzinger, Christoph
Müller, Tobias
author_facet Aupperle-Lellbach, Heike
Heidrich, Daniela
Kehl, Alexandra
Conrad, David
Brockmann, Maria
Törner, Katrin
Beitzinger, Christoph
Müller, Tobias
author_sort Aupperle-Lellbach, Heike
collection PubMed
description SIMPLE SUMMARY: It is well known that dark-coated dogs, especially schnauzers, have a predisposition for digital squamous cell carcinoma (dSCC). Molecular genetic studies by other researchers indicate a pathogenetic role of copy number variations (CNVs) of the KIT ligand (KITLG) gene. Our study aimed to use droplet digital PCR of blood samples to investigate whether the copy number has a predictive value for the disease in schnauzer breeds. We showed that most giant (GS), standard (SS), and miniature schnauzers (MS) had more than four and up to seven copies of this gene segment. Furthermore, the copy number in black GS with dSCC was significantly higher than in the black control GS (p = 0.02). CNV values > 5.8 indicate a significantly increased risk for dSCC, while a reduced risk can be assumed for GS with CNV < 4.7. CNV values between 4.7 and 5.8 appear as a grey area. In summary, including the germline mutation (KITLG CNV) in breeding decisions will be complex, but this diagnostic test may help to assess the individual risk for dSCC and to sensitise owners of black GS accordingly if the CNV value is high. ABSTRACT: Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5–7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7–5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC.
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spelling pubmed-99667982023-02-26 KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers Aupperle-Lellbach, Heike Heidrich, Daniela Kehl, Alexandra Conrad, David Brockmann, Maria Törner, Katrin Beitzinger, Christoph Müller, Tobias Vet Sci Article SIMPLE SUMMARY: It is well known that dark-coated dogs, especially schnauzers, have a predisposition for digital squamous cell carcinoma (dSCC). Molecular genetic studies by other researchers indicate a pathogenetic role of copy number variations (CNVs) of the KIT ligand (KITLG) gene. Our study aimed to use droplet digital PCR of blood samples to investigate whether the copy number has a predictive value for the disease in schnauzer breeds. We showed that most giant (GS), standard (SS), and miniature schnauzers (MS) had more than four and up to seven copies of this gene segment. Furthermore, the copy number in black GS with dSCC was significantly higher than in the black control GS (p = 0.02). CNV values > 5.8 indicate a significantly increased risk for dSCC, while a reduced risk can be assumed for GS with CNV < 4.7. CNV values between 4.7 and 5.8 appear as a grey area. In summary, including the germline mutation (KITLG CNV) in breeding decisions will be complex, but this diagnostic test may help to assess the individual risk for dSCC and to sensitise owners of black GS accordingly if the CNV value is high. ABSTRACT: Copy number variations (CNVs) of the KITLG gene seem to be involved in the oncogenesis of digital squamous cell carcinoma (dSCC). The aims of this study were (1) to investigate KITLG CNV in giant (GS), standard (SS), and miniature (MS) schnauzers and (2) to compare KITLG CNV between black GS with and without dSCC. Blood samples from black GS (22 with and 17 without dSCC), black SS (18 with and 4 without dSSC; 5 unknown), and 50 MS (unknown dSSC status and coat colour) were analysed by digital droplet PCR. The results are that (1) most dogs had a copy number (CN) value > 4 (range 2.5–7.6) with no significant differences between GS, SS, and MS, and (2) the CN value in black GS with dSCC was significantly higher than in those without dSCC (p = 0.02). CN values > 5.8 indicate a significantly increased risk for dSCC, while CN values < 4.7 suggest a reduced risk for dSCC (grey area: 4.7–5.8). Diagnostic testing for KITLG CNV may sensitise owners to the individual risk of their black GS for dSCC. Further studies should investigate the relevance of KITLG CNV in SS and the protective effects in MS, who rarely suffer from dSCC. MDPI 2023-02-11 /pmc/articles/PMC9966798/ /pubmed/36851451 http://dx.doi.org/10.3390/vetsci10020147 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Aupperle-Lellbach, Heike
Heidrich, Daniela
Kehl, Alexandra
Conrad, David
Brockmann, Maria
Törner, Katrin
Beitzinger, Christoph
Müller, Tobias
KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title_full KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title_fullStr KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title_full_unstemmed KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title_short KITLG Copy Number Germline Variations in Schnauzer Breeds and Their Relevance in Digital Squamous Cell Carcinoma in Black Giant Schnauzers
title_sort kitlg copy number germline variations in schnauzer breeds and their relevance in digital squamous cell carcinoma in black giant schnauzers
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9966798/
https://www.ncbi.nlm.nih.gov/pubmed/36851451
http://dx.doi.org/10.3390/vetsci10020147
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